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Pancreatic ductal adenocarcinoma is associated with a unique endocrinopathy distinct from type 2 diabetes mellitus
Sajan Jiv Singh Nagpal1, Harika Kandlakunta2, Tracy Her3
1Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, UChicago Medicine, Chicago, IL, USA.
Introduction:
The majority of patients with pancreatic ductal adenocarcinoma (PC) display either impaired fasting glucose/glucose intolerance or overt diabetes. However, the pathophysiologic basis of this association remains largely unexplained.
Methods:
In this case-control study we aimed to study the morphological changes in the islets of patients with PC, compared to control patients with and without type 2 diabetes mellitus (T2DM). T2DM controls and PC cases had a lower β-cell area and average islet size and density compared to non-T2DM controls (p < 0.05).
Results:
Compared to both T2DM and non-T2DM controls, mean α-cell area was significantly lower and β/α-ratio was higher in PC cases (p < 0.05). Furthermore, whereas islets in T2DM controls were characterized by disrupted islet architecture and presence of islet amyloid aggregates, islet composition in PC islets was not significantly different compared to non-T2DM controls (p > 0.05 vs. Control).
Conclusions:
Our data shows that PC is associated with a unique pattern of islet pathology characterized by preserved architecture, absence of amyloid aggregates, and relative α-cell loss indicating that distinct mechanisms are likely involved in the pathophysiology of islet failure in PC-induced DM. Insights into the mechanisms mediating β-cell failure in PC can be important for our understanding of pathophysiology of PC.
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